In recent years there has been great interest in finding methods of releasing active agents from chewing gum in a controlled manner. The extensive interest is both due to the wish to use chewing gum as a delivery system, for instance for drugs, and the wish to be able to release costly ingredients, such as flavours (aromas) and highly potent (or intensive) sweeteners, in moderate quantities during the relatively short chewing period.
Many factors determine the extent and speed of the release of a substance from a chewing gum. A decisive feature is the solubility of the substance. A substantially water-soluble substance is thus usually released quickly, whereas a substantially fat-soluble substance is bound more or less firmly to the water-insoluble ingredients of the chewing gum, the latter causing a slower and sometimes insufficient release during the usual chewing period.
The ratio of soluble to insoluble ingredients in the chewing gum composition, the size of the chewing gum piece, as well as the chewing intensity and the secretion of saliva of the chewer are also of importance to the release. Usually it is neither possible nor desirable to alter the latter factors.
Therefore it is necessary to involve other methods when it is desired to influence the release. In general, such methods aim at influencing the dissolution rate of the substance by coating, absorption or adsorption or by encapsulation in other materials. Hydrophilic compounds can be used for substances of a poor water-solubility as a means for achieving an improved and faster release. Examples of such substances with relatively limited solubility are for instance flavourings and relatively sparingly soluble sweeteners having a strong sweetening effect such as saccharine and aspartame, as well as many drugs.
It is a well-known problem in chewing gum preparation that only a small share of the aroma agents added are released from the chewing gum within the ususal chewing period of 2 to 10 minutes. It is not unusual that the amount of aroma agent relased stated as a percentage of the total quantity of aroma agent added, is of the following order:
After chewing for 2 minutes: 5 to 15% PA1 After chewing for 5 minutes: 7 to 20% PA1 After chewing for 10 minutes: 10 to 25%
Which means that a very large share, 75 to 90% of the aroma agents added is wasted when the chewing gum is thrown away. This is the reason why a relatively large quantity of aroma agents is used in chewing gum compared to other confectioneries. The aroma agents often being costly ingredients, the quantity of these in a chewing gum composition, although usually only present in a quantity of around 0.5 to 2.0%, is of great importance to the price and consequently to the competitiveness of the product.
In recent years extensive research has been carried out with respect to the use of chewing gum as a delivery system for medicines. This delivery system has proven especially suitable when a local effect in the oral cavity or the pharynx is desired or when an absorption of the medicine via the mucous membrane of the mouth is required in such cases when it is desirable to avoid the so-called "first pass" effect, that is the catabolism in the liver at the first passage, or when the medicine is sensitive to the environment in the gastro-intestinal tract.
Several methods have been provided for the preparation of a chewing gum composition capable of releasing specific components in a controlled manner. Thus, a number of processes are known for obtaining an improved release of specific aroma agents and highly potent sweeteners with the purpose of prolonging the perception of taste when chewing a chewing gum.
U.S. Pat. No. 4,238,475 discloses a chewing gum comprising a water-insoluble thereapeutic component which is coated with a water-soluble coating agent to prevent resorption of the therapeutic component back into the gum base. The release of the therapeutic component is, however, conditional on the coating remaining intact during the chewing. As a result, the therapeutic component does not come into direct contact with the oral cavity and cannot therefore be used for medicines intended to be locally effective in the oral cavity and the pharynx. Furthermore, the method of preparation is elaborate and further complicated by the fact that the coating must not be destroyed during the preparation.
EP patent application No. 227,603 discloses a chewable delivery system comprising an active agent coated with lecithin, polyoxyalkylene, glyceride etc and then incorporated in a matrix system comprising among other things gelatine, water and sweetener. Also in this case the active agent passes through the oral cavity in a coated form and will therefore not produce a local effect.
EP patent application No. 229,000 discloses a process and a chewing gum for the protection and controlled release of an active agent, including medicine, highly potent sweeteners and aroma agents. The active agent is provided with a hydrophobic coating using a melt blend of polyvinyl acetate and plasticizer whereupon the blend is cooled, ground, sieved and blended with usual chewing gum ingredients. It is stated chat a delayed release in the order of 10 to 20 minutes can be obtained, but this does, however, not automatically result in an increase of the total quantity of substances released. The process is rather complicated and requires the active agent To be able to stand the temperatures involved in the process.
EP patent application No. 217,109 discloses a chewing gum in which prolonged and controlled release of, among other things, pharmaceutical agents, food ingredients and confectionery ingredients in multi-micro encapsulation hereof is obtained by means of, for instance, cellulose compounds, polyvinyl pyrrolidone, starch or saccharose etc. The process is, however, complicated and difficult to control.
U.S. Pat. Nos. 4,493,849 and 4,597,970 disclose that lecithin can be used in chewing gum to improve the mouth-feel of the chewing gum and to increase the moistening properties and texture.
U.S. Pat. No. 4,518,615 discloses a chewing gum base composition that does not adhere to dentures, removable and fixed oral prostethic devices, filings or natural teeth, said chewing gum base composition including in weight percent about 10-30% elastomer, 2-18% elastomer solvent, 15-45% polyvinyl acetate, 2,0-10% emulsifier, 0,5-15% low molecular weight polyethylene, 0,5-10% waxes, 10-40% plasticizer and 0-5% fillers.
DK patent application No. 5386/83 discloses a method for obtaining longer impact times in The oral cavity when treating fungal infections in the oral cavity. This is obtained by formulating antifungally active compounds, especially imidazole and triazole derivatives, with special gel agents such as cellulose ethers, sodium alginate and propyleneglycol alginate, in order to obtain a better adhesion of the active agent to the oral cavity. It is, however, unpleasant and difficult to keep such gelatinous preparations in the mouth for long and the impact of the active agent will vary considerably depending on how long it is kept in the mouth.
U.S. Pat. No. 4,514,382 discloses a method for solubilization of the water-insoluble antigingivitis agent, imidazolyl-1,1-(p-chlorophenoxy)-3,3-dimethyl 2-butanone, in oral compositions. Mouth rinses, chewing gum, tooth powder and tooth paste are mentioned as oral compositions, but only the use in mouth rinses and tooth paste is documented. If, on the basis of what is stated in the above U.S. patent, a person skilled in the art attempts to prepare a chewing gum with the amounts of solubilizer stated, it will be seen for most gum bases that the chewing gum base is also solubilized, which means that the chewing gum disintegrates when chewed and is thus totally unacceptable.
Thus, there is still a need for an acceptable chewing gum composition which can deliver an active agent of relatively limited solubility to be effective locally in the oral cavity or the pharynx or to be absorbed through the mucous membrane of the mouth, while still being pleasant to take or use, whether a medical effect or a relishing effect is desired as in the cases where the active agent is for instance a medicine or an aroma agent, respectively.
Surprisingly, it has been found that it is possible to obtain a chewing gum composition with accelerated controlled release of active agents comprising one or more active agents, a particular selected chewing gum base and usual auxiliary agents and additives.